Development of a novel treatment for muscle atrophy based on the elucidation of the mechanism of sarcomere synthesis.

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K15130
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Juntendo University
• Principal Investigator: Hayashiji Nozomi 順天堂大学, 医学部, 特任助教 (80772433)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: サルコメア / 顆粒球コロニー刺激因子 / 糖鎖修飾 / 糖鎖合成酵素 / Fucosyltransferase 8

Outline of Final Research Achievements

Sarcomeres are the smallest contractile organs of skeletal muscle. Skeletal muscle mass is regulated from time to time by the synthesis and degradation of sarcomeres in response to nutritional status and exercise load. The aim of this study was to elucidate the mechanism of sarcomere synthesis and to identify molecules that promote muscle mass gain.
This study focused on the fact that granulocyte colony-stimulating factor (G-CSF) deficiency leads to sarcomere structural instability and synthesis resistance, and found the glycosyltransferase Fucosyltransferase 8 (Fut8) as a factor involved in sarcomere stabilisation. Furthermore, L-fucose was identified as a factor that enhances the function of FUT8 and was found to be effective both in vitro and in vivo.

Free Research Field

骨格筋再生

Academic Significance and Societal Importance of the Research Achievements

骨格筋は、運動機能としての役割だけでなく代謝や恒常性の維持など生存に重要な様々な機能を担っている。近年、骨格筋量は健康寿命やがんの予後などに正の相関にあり、骨格筋量そのものを保つことが重要であることが相次いで報告された(BMJ 2008; BMJ 2012)。しかし、骨格筋量を規定する機構は十分に解明されておらず、現在のところアミノ酸・タンパク質の摂取や運動療法以外有効な因子の特定には至っていない。以上のことから、骨格筋量を規定する因子を明らかとする本研究は、学術的のみならず社会的意義においても非常に重要な課題である。